Rodrigues: Are you saying that work helped to define the understanding
of the component of the immune system that made those responses possible?
If someone told you at that point that HIV was knocking out that particular
cell, would you have known that that was the reason that there was this
complete lack of immune response, or was the role of that particular cell
not known yet?

Lane: I would say that the level to which that cell population was affected
was not understood at that time. We knew the numbers were down, but we
didn't know that there was not only a decrease in numbers, but really
a selective and very precise functional abnormality in the cells of these
patients. Now, there is a ton of literature proposing hundreds of hypotheses
describing thousands of immunologic quirks of these patients. You take
the T helper-inducer cell and you eliminate it, and it's sort of like
taking a symphony orchestra and shooting the conductor and not telling
them the score to play, and then saying, “O.K., play.” So some
people are playing Beethoven and some people are playing Schoenberg; the
thing is all discombobulated, and that's what happens in AIDS patients.
The helper-inducer cell can't recognize specific antigen, as a result
of which it can't call different elements of the immune system into play
the way it should.

Harden: Is there some reason it can't recognize it, other than because
it's been destroyed?

Lane: That's
still unclear. It appeared that the memory subset of CD4 T cells is selectively
destroyed by HIV. That's the way it appears right now. So it not only
hits the T helper cell; it hits just that part of the helper cell you
need to respond to recall antigens at the T-cell level. Everyone is probably
exposed to Candida and Pneumocystis early in life and
has memory cells to them. You have to believe that they are not well-described,
because with these suppressed T cells, why do you get such profound problems
with those [infectious] agents–not just in AIDS patients but in
other patient groups as well.

Rodrigues: I think it's interesting the way you describe the different
types of collaborations that are going on here–you mention folks
in Critical Care Medicine; you mention folks in the National Cancer Institute.
Some of the people that look at NIH from the outside don't appreciate
the diversity; they tend to compartmentalize people in groups. Could you
say a little bit about...

Lane: Sure. The
early days of AIDS were great in that regard. The early days were really
very nice because everyone was excited and everyone wanted to figure out
what was going on. Everyone had their own different little area of expertise.
[Dr.] Henry Masur had taken care of AIDS patients in New York and he was
here. Over at the FDA, a guy named [Dr.] Alain Rook, working with Jerry
[Dr. Gerald] Quinnan, had expertise in cytomegalovirus and the immune
response to cytomegalovirus. They were interested in studying the AIDS
patients as well. You had people like myself who were immunology-oriented.
There were people from the Cancer Institute–Ed [Dr. Edward] Gelmann,
who had been in Bob Gallo's lab working on HTLV-1, had left Bob and was
over here [in the Clinical Center], with an interest in the retrovirally
induced diseases. He was working on AIDS before we knew it was a retrovirus.
And there were people like [Dr.] Dan Longo, who were a little bit more
peripheral at that point in time. Dan was interested in lymphomas and
chemotherapeutic regimens, trying to make some contributions. So, there
were a lot of people with different backgrounds coming in who were thrown
together–not just from NIH, but from the FDA as well. [Dr.] Abe
Macher, who was down in Anatomic Pathology at that time, had a strong
interest in what was going on. Abe is one of the people who was bringing
cadavers in to try to understand the disease. He would bring cadavers,
from all round the country, to try to see what kinds of problems the patients
had died of. He was doing his fellowship in pathology at that time. He
had already done a fellowship in infectious diseases. There was a lot
of interaction like that. That was a good time, I think.

Rodrigues: Sounds as if there was an informal network of people that
gradually came together.

Lane: Exactly, exactly.

Harden: Was there any connection with people at the CDC [Centers for
Disease Control and Prevention] on AIDS–or were they basically doing
epidemiology, and therefore, not seeing clinical patients?

Lane: Well, while they weren't seeing patients, they certainly were
doing their own research. But until we had a virus, it was a lot of shots
in the dark. I would see them at meetings. The meetings were so different;
the meetings were small. The meetings were small and they were fairly
intimate, where there were good exchanges of information. There you would
interact with the CDC people. I can't remember talking with anyone from
CDC up here myself. But then we weren't doing things that really were
pertinent to them. When we had the virus, the guys from the CDC were up
here all the time, talking to Bob [Dr. Robert] Gallo about samples of
some coded sera and what he could tell from those sera. I remember seeing
them in the cafeteria and talking to them about what was going on. They
were very excited.

So, it was, as you say, sort of an informal network of people who began
to interact. Those of us who were taking care of patients started to have
weekly meetings where we got together, and we started to use some electronic
databases to keep track of what was going on. Then it started to expand.
The guys in the NCI [National Cancer Institute] were initially looking
at lymphoblastoid interferon to treat KS, Kaposi's sarcoma, and I was
doing the immunologic monitoring on those patients. It worked out well,
because it was the sort of thing where one person couldn't have set it
up because it requires too many things, but we had people who knew enough
about the different pieces. We needed oncology, we needed infectious diseases,
we needed immunology–and we had all of that here. We just fit the
pieces in, and I think made a lot of progress pretty quickly.

Harden: I think one of the things that we are very interested in is trying
to get a picture of just how this process worked, because I think many
people and journalists don't have a sense of how it works. They have a
sense that perhaps the way the government deals with things and should
deal with things is by appointing a committee that will then direct things.
This is not what we are hearing.

Lane: Oh, not at all.

Harden: It begins at the grassroots. Everybody finding people when they
needed them.

Lane: We did that because we wanted to do it. No one said to me: “Listen,
you have to work on AIDS now.” No one said that. The people were
here because they wanted to [work on HIV/AIDS]. That's your best incentive
to get people doing something that they like and they enjoy. As I say,
it was just the right mix needed to get a productive effort going. There
was a lot of collegiality; Henry [Dr. Henry Masur] and I still work very
closely together. We built the NIAID intramural clinical program. It's
my program and his program that stemmed from all of that. NCI had to develop
their own intramural clinical program as that process evolved. But some
of those things still exist from the past.

Harden: Did you have any trouble getting support from Ken [Dr. Kenneth]
Sell and [Dr.] John Gallin over this period?

Lane: It was
great. I can remember, when you say the word “bone marrow transplantation,”
you think of a lot of money. Here, it was no money at all, because no
one was charging anything. We got the beds and everything else. It was
sort of a fixed cost for us, the way we work. When it came to the interleukin-2,
I can remember calling this person or calling that person. Finally after
getting this astronomical figure, I remember talking to Tony [Dr. Anthony
Fauci]. I said, “Well, let's go talk to Ken Sell.” Ken was
here at NIH. He was good; he made a great contribution that I don't know
will ever get recognized, because it wasn't a publication or anything
like that. But he saw the importance of AIDS. He put the resources into
it. We went down to his office and explained to him why we wanted to use
this [interleukin-2]. He said, “ Two-hundred-and-fifty-thousand
dollars–well, sounds like it should be done. We'll do it.”
I don't know if you went over to Dick [Dr. Richard] Krause and Chuck [Charles]
Leasure, who was the executive officer at that time. I don't know where
the money came from; it wasn't from a Congressional appropriation. Somewhere
there was the money and we were able to get it. It wasn't a problem. Do
you know Ken? Have you talked to him?

Harden: Yes.

Lane: So he got the lab going over there; he brought the people over
to culture LAV [lymphadenopathy-associated virus]; he put the resources
in to get the thing. He really played a major role in getting the Institute
galvanized. It was my perception that he was instrumental in getting this
MACS [Multicenter AIDS Cohort Studies] work going. He said that we needed
to look at these people. This was before HIV. This is not my approach
to science–“Hey, I don't know what it is, but let's get 6,000
gay men and collect every secretion from their body and freeze it, and
some day it will be useful.” But that's important to do. You need
someone at that high a level to get it done. He was very instrumental
and very supportive. I give him a lot of credit. It's a tough position.
Everybody wants something from the scientific director. He clearly made
this priority, and I was impressed by that.

Rodrigues: Do you remember any particular meetings at that time that
were important in helping you make intellectual progress on these problems?
We've heard people mention a number of meetings. There was one meeting
in New York, I believe in 1982, that people have talked about as a very
important meeting.

Lane: I think I know what meeting it was. The New York Academy of Sciences?
I think these are the proceedings from that meeting. I didn't find that
meeting to be particularly enlightening, to be honest. I found that meeting
to be anecdotal. But it was the first time, I think, that a large group
was brought together to discuss the problem. I was at that meeting, but
I just didn't get that much out of it. I generally knew what was being
said, because it wasn't a very scientific meeting. What I'm saying is
that there was a lot of description. This is what Kaposi's sarcoma looks
like. This is what Pneumocystis carinii pneumonia is. But then what? I
guess that was all that could have been said. I wouldn't say that was
a key point in my academic development.

Now, a meeting that was important, and people will probably mention,
is the Cold Spring Harbor meeting shortly thereafter. That was a group
that [Dr.] Bijan Safai put together. I don't have the proceedings from
that. I don't know whether there were proceedings from that. That was
the first time people talked about a retrovirus. Some people from [Dr.
Luc] Montagnier's group presented some data, saying that this might be
something. [Dr. Robert] Gallo was there presenting the stuff they had
at that time on HTLV-I and serologic cross-reactivity. We presented the
polyclonal B-cell activation for the first time there. There were a lot
of things, as you start to think more. We were talking about acid-labile
interferon being elevated–a lot of things that weren't generally
known were coming out in discussion. It was a fairly informal setting.
We met, had presentations, discussion, ate meals with these same people.
We were there for about two-and-one-half days. I remember driving in from
New York. It was snowing very heavily. I was in the cab with Marty [Dr.
Martin] Hirsch who is a virologist from Massachusetts. I just can't think
who the other person was. There were three of us in the cab. It was snowing
so hard that the cab driver had to pull over, so he took us all out to
a bar. We were sitting there discussing AIDS, well, trying to, because
we didn't know anything about AIDS then. We had seen a few patients at
most. But I remember those times so vividly.